|ZFIN ID: ZDB-PUB-180830-10|
An automated screening method for detecting compounds with goitrogenic activity using transgenic zebrafish embryos
Jarque, S., Fetter, E., Veneman, W.J., Spaink, H.P., Peravali, R., Strähle, U., Scholz, S.
|Source:||PLoS One 13: e0203087 (Journal)|
|Registered Authors:||Peravali, Ravindra, Spaink, Herman P., Strähle, Uwe|
|PubMed:||30157258 Full text @ PLoS One|
Jarque, S., Fetter, E., Veneman, W.J., Spaink, H.P., Peravali, R., Strähle, U., Scholz, S. (2018) An automated screening method for detecting compounds with goitrogenic activity using transgenic zebrafish embryos. PLoS One. 13:e0203087.
ABSTRACTThe knowledge on environmentally relevant chemicals that may interfere with thyroid signaling is scarce. Here, we present a method for the screening of goitrogens, compounds that disrupt the thyroid gland function, based on the automatic orientation of zebrafish in a glass capillary and a subsequent imaging of reporter gene fluorescence in the thyroid gland of embryos of the transgenic zebrafish line tg(tg:mCherry). The tg(tg:mCherry) reporter gene indicates a compensatory upregulation of thyroglobulin, the thyroid hormone precursor, in response to inhibition of thyroid hormone synthesis. Fish embryos were exposed to a negative control compound (3,4-dichloroaniline), or a concentration series of known goitrogenic compounds (resorcinol, methimazole, potassium perchlorate, 6-propyl-2-thiouracil, ethylenethiourea, phloroglucinol, pyrazole) with maximum exposure concentration selected based on mortality and/or solubility. Exposure to 3,4-dichloroaniline decreased the fluorescence signal. All goitrogenic compounds exhibited clear concentration-dependent inductions of reporter fluorescence 1.4 to 2.6 fold above control levels. Concentration-response modelling was used to calculate goitrogenic potencies based on EC50 values. The new automated method offers an efficient screening approach for goitrogenic activity.